Decreased expression of XPO4 is associated with poor prognosis in hepatocellular carcinoma

Background and Aim: Exportin 4 (XPO4) is a recently-discovered candidate tumor-suppressor gene identified in a liver cancer mouse model. To investigate the role of XPO4 in hepatocellular carcinoma (HCC) pathogenesis, we determined XPO4 expression and its correlation to prognosis in human primary HCC. Methods: The XPO4 mRNA transcription level in HCC cell lines and tissue samples were detected by real-time quantitative polymerase chain reaction (PCR). XPO4 protein expression in 123 primary HCC clinical surgical specimens were analyzed by immunohistochemical detection. Results: Real-time quantitative PCR showed a decrease in XPO4 expression in HCC cell lines BEL-7402, Hep-G2, and SK-hep1 compared to the normal liver cell line LO2. Decreased XPO4 mRNA was also found in the majority of tumor tissues compared with matched non-tumor liver tissues (P = 0.004). Immunohistochemical detection revealed that XPO4 expression was reduced in 51 of 123 (41.5%) tumor resection samples compared with adjunct non-tumor tissues. We also found XPO4 expression to be significantly correlated with tumor size (P = 0.045) and histopathological classification (P = 0.004). Kaplan-Meier survival curves showed that the downregulation of XPO4 resulted in a significantly poor prognosis (P = 0.008, log-rank test), and multivariate Cox's analysis showed that XPO4 expression was an independent prognostic factor for overall survival of HCC patients (P = 0.013). Conclusions: Our data suggest that XPO4 could be involved in the progression of human HCC and could serve as a potential target for gene therapy in the treatment of HCC.